3.19.2010<br /><ul><li>Small G proteins are single monomer proteins that bind GDP or GTP, GEFS help exchange GDP for GTP. GAPs enhance inactivation state on small g proteins, examples include… all regulated like a switch.
Cytosolic side of receptor is the binding site for heterotrimeric g proteims, which contains a loop between strands 5 and 6 and ligand binding domain is between 6 and 7. – extracellular
When ligand binds to it, it exposes an activation site (binding site) for heterotrimeric g proteins, which is linked to the membrane (meristic acid that links protein to membrane) and when exposed, interacts with HTGP
Once the alpha subunit is removed, the enzyme is inactive. When the alpha subunit is bound to GDP, it no longer associates with the enzyme and it exposes binding sites for B/G subunit, so they can all come together.
cAMP binds to a kinase, called protein Kinase A, which sits in cytosol in inactive state until bound by cAMP. Similar to cGMP. PKG and PKA both have a structure so they have regulatory sites that can be bound by an intracellular signaling protein
when they are bound, open up and release catalytic site that does the phosphorylating.
cGMP, activates PKG, synthesized by guanylyl cyclase
for PKA, two molecules of cAMP must bind to activate
G protein linked receptor that binds ligand will have a heterotrimeric g proteinactive
Activated alpha will move through membrane and activate PLCB that exposes cleavage site that can cleave phosphoinositol bisphosphosphate into DAG and IP3 signaling molecule
As IP3 moves to receptors on intracellular Ca2+ storage sites, it binds to IP3 receptors and it itself opens up and allow calcium to move to the cytosol. (it is an ion channel, the receptor)
DAG and Ca2+ will activate PKC inside the cell.
PKC enzyme phosphorylates serine and threonine is activated by DAG in phospholipid bilayer, binding of PS (phosphatidalserine, inserted in PM and flipped to inner leaflet) in the lipid bilayer and the binding of calcium that is required for activation of PKC
IP3 signaling pathway is a main way that levels of Ca2+ increase for active PKC
Very local signaling molecule, will happen right on the PM etc
Calmodulin has a complex carboxy and amino termini. Within globular ends, there are two binding sites for calcium so four calcium molecules are bound by calmodulin in cytoplasm and is then activated
Once activated can form kinase, which can wrap itself around a phosphorylating enzyme and stays attached to it. Ca calmodulin complex is PART OF THE KINASE SO IT CANNOT FUNCTION WITHOUT THE ENZYME